InterceptingHost Microbial Signalling for Prevention of Chronic Pathogen Establishment in Respiratory Disease Microbiomes .

Despite aggressive antimicrobial therapy, many respiratory pathogens persist in the lung, underpinning the chronic inflammation and eventual lung decline that are characteristic of respiratory disease. Early clinical interventions that prevent pathogens from entering this chronic persistent lifestyle are key to the effective management of chronic infections and associated inflammation. Recently, bile acid aspiration has emerged as a major comorbidity associated with a range of lung diseases, shaping the lung microbiome and promoting colonisation by Pseudomonas aeruginosa in Cystic Fibrosis (CF) patients. Bile signaling was shown to elicit chronic biofilm behavior and modulate antibiotic tolerance in respiratory pathogens, including P. aeruginosa and Staphylococcus aureus, suggesting adaptation of the host microbiome to the presence of this important host factor. Global expression profiling and functional genomics revealed insights into the molecular mechanism underlying this response. Therapies that prevent the aspiration of this key host trigger into the lungs of patients with respiratory disease could be effective in combatting the onset of chronic disease. Furthermore, the tandem development of small molecular therapeutics that intercept the formation of biofilms by microbial pathogens, without disturbing the homeostasis of the host microbiome, is of crucial importance.